Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.     

肺内源性和肺外源性呼吸衰竭机械通气的临床对比研究

目的探讨肺内源性和肺外源性呼吸衰竭机械通气时的肺保护性策略。方法通过25例呼吸衰竭中12例肺内源性和13例肺外源性机械通气临床资料的回顾性分析,对比研究两组呼吸力学差异时对通气模式选择、参数设置和调节的影响,以及肺保护的实施方法。结果在两组APACHE-Ⅱ评分、平均年龄和Vt设置无差异的条件(P>005)下,肺内源性组PEEP/CPAP、PSV、f的需设值均明显高于肺外源性组(P<001)。肺内源性组Pplat、PIP、Raw的监测结果大于肺外源性组,而Crs小于肺外源性组(P<001)。肺内源性组417%和肺外源性组154%因MOF而死亡(APACHE-Ⅱ评分均>20分),组间比较有显著差异(P<001)。结论肺内源性和肺外源性呼吸衰竭机械通气时,实施肺保护的方法不同。前者应首选压力预置通气模式,后者可首选容量预置通气模式。以设置中、小Vt为原则,按个体化的通气需求而设置f和加用恰当的PSV、CPAP/PEEP对减少VILI、病死率可能有益。     

Effects of tracheal extubation on coronary blood flow,myocardial metabolism and systemic haemodynamic responses

Global coronary blood flow and metabolism were measured in seven patients on the first postoperative day following coronary revascularization to test the hypothesis that tracheal extubation produces adverse haemodynamic responses akin to those observed during tracheal intubation. Regional coronary flow and metabolic measurements were made in five of the seven patients. Extubation from a continuous positive airway pressure (CPAP) of 5 cm H₂O was associated with a statistically significant rise in cardiac index from 3.44 ± 0.23 L · min^-1 · m^-2 to 3.73 ± 0.15L·min^-1 ·m^-2 related to an increase in stroke index, without significant changes in heart rate, mean arterial and pulmonary capillary wedge pressure. Consequently the changes in myocardial oxygen consumption (8.52 ± 0.55 to 8.85 ± 0.93 ml · min^-1) and coronary blood flow (172 ± 18 to 179 ± 17 ml·min^-1) were less prominent than those reported during intubation, where substantial rises in myocardial oxygen consumption and coronary flow occurred. Two patients experienced cardiac lactate production but there were no changes in systemic or coronary haemodynamics, nor were there clinical or electrocardiographic signs of ischaemia. We conclude that extubation does not appear to be associated with adverse systemic or coronary haemodynamic responses in patients following coronary bypass grafting. However, the revascularized myocardium may remain vulnerable to anaerobic metabolism in the immediate postoperative period. Pour savoir si comme ľintubation, ľextubation de la trachée provoque des perturbations hémodynamiques, on a mesuré le métabolisme et la circulation coronarienne globale chez sept patients, au lendemain ďun pontage aorto-coronarien. On a aussi calculé les valeurs régionales de ces mêmes variables pour cinq ďentre eux. Ľindex cardiaque de 3.44 ± 0.23 L · min^-1 · m^-2 sous pression positive en respiration spontanée (CPAP) de 5 cm. H₂O s’est élevé à 3.73 ± 0.15 L · min^-1 · m^-2 post-extubation avec une augmentation significative du volume ďéjection. La fréquence cardiaque et les pressions artérielles moyennes et capillaires pulmonaires n’ont pas changé. Ainsi ľaugmentation de la consommation ďoxygène du myocarde de 8.52 ± 0.55 à 8.85 ± 0.93 ml · min^-1 et celle du flot coronarien de 172 ± 18 à 179 ± 17 ml · min^-1 ont été moindres que celles, importantes, déjà observées lors de ľintubation. On a noté chez deux patients une production de lactate par le myocarde, sans changement de ľhémodynamic systémique et coronarienne non plus que de signe clinique ou électrocardiographique ďischémie. Donc, après un pontage coronarien, ľextubation ne semble pas causer ďeffet néfaste sur les circulations systémique et coronarienne, toutefois, le myocarde revascularisé peut demeurer sensible au métabolisme anaérobique.     

42例室性心动过速治疗的临床分析

本文介绍了42例室性心动过速的临床资料和特点,讨论了早期后除极与室性心动过速的关系,并探讨各型室速的治疗。     

中药高臀位灌肠治疗慢性肾功能衰竭疗效观察

目的 观察中药高臀位灌肠治疗慢性肾功能衰竭(chronic renal failure,CRF)的临床疗效.方法 将100例CRF患者随机分为两组,治疗组70例采用中药高臀化灌肠治疗,对照组30例口服活性炭治疗.结果 治疗组总有效率为88.6%,对照组总有效率为50.0%.结论 中药高臀位灌肠治疗CRF有效.     

Cardiac metastasis of renal pelvic cancer

Abstract:   A 66-year-old man was referred to our hospital with chest discomfort and shortness of breath. Seven months previously he had undergone a laparoscopic left nephroureterectomy for a left renal pelvic tumor and was given two cycles of adjuvant chemotherapy (methotrexate, epirubicin and cisplatin). Echocardiogram showed an 8-mm sized mass extending from the right atrium into the right ventricle. On computed tomography, multiple lung tumors, as well as the right atrial and ventricular mass, were seen. The patient died of acute heart failure caused by right ventricular outflow obstruction. On autopsy, a right atrial and ventricular metastasis of the initial transitional cell carcinoma was found. The patient's cause of death was acute heart failure as a result of cardiac metastasis of his initial renal pelvic carcinoma.     

肺心病合并脑梗死39例分析

目的:分析肺心病合并脑梗死的临床特点.方法:对39例肺心病合并脑梗死患者的临床资料进行回顾性分析.结果:肺心病合并脑梗死发病率6.2%,48小时内确诊率48.7%.结论:肺心病合并脑梗死临床表现不典型,及时确诊困难.     

生脉注射液对慢性心力衰竭患者凝血功能的影响

目的研究大剂量生脉注射液对慢性心功能衰竭（简称心衰）患者凝血功能的影响。方法将60例慢性心衰患者随机分为治疗组（即生脉注射液组）和对照组，每组各30例，治疗组给予生脉注射液加西药常规治疗，对照组仅西药常规治疗，观察用药前后心功能改善程度及血浆P-选择素、血管性血友病因子（vWF）和D-二聚体水平的变化。结果治疗组临床显效率与总有效率明显高于对照组。心是患者血浆P-选择素、vWF和D-二聚体水平明显高于健康人，治疗后两组患者血浆P-选择素、vWF和D-二聚体水平均下降，治疗组优于对照组。结论慢性心衰患者，体内存在着高凝状态，大剂量生脉注射液可改善慢性心衰患者的凝血功能，可能在一定程度上减少心衰患者血栓事件的发生和发展？     

不同免疫剂治疗扩张型心肌病患儿心功能和临床预后评价

目的观察比较泼尼松联用硫唑嘌呤和大剂量静脉用免疫球蛋白(IVIG)对扩张型心肌病(DCM)患儿心功能及预后的影响。方法将DCM患儿20例分为治疗Ⅰ和Ⅱ组,分别在传统抗心衰治疗基础上加泼尼松联用硫唑嘌呤和大剂量IVIG,治疗1个疗程后评价心功能,检测治疗前后左房横径(LA)、左室舒张期内径(LV)、左室射血分数(LVEF)、心脏指数(CI),并计算其治疗前后变化。所有病例随访1年,计算1年存活率。结果治疗Ⅱ组心功能明显优于治疗Ⅰ组(P均<0.05);两组LA、LV、LVEF和CI治疗后较治疗前均有明显改善(P均<0.05);治疗Ⅰ组各参数变化明显低于治疗Ⅱ组(P均<0.05),其1年存活率明显低于治疗组Ⅱ(P<0.05)。结论泼尼松联用硫唑嘌呤和大剂量IVIG均能改善DCM患儿心功能,但IVIG疗效优于泼尼松联用硫唑嘌呤。     

Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease

OBJECTIVES: To determine if polymorphisms of the tissue plasminogen activator (t-PA) gene influence acute endogenous t-PA release in patients with coronary heart disease (CHD). METHODS: Forearm blood flow and plasma t-PA concentrations were measured in response to intra-brachial infusion of substance P and sodium nitroprusside in 96 patients with stable CHD. Genotyping was performed using a Taqman polymerase chain reaction assay specifically designed to detect the polymorphisms of interest: (i) Alu-repeat insertion/deletion sequence; (ii) C-->T substitution in an upstream enhancer region (-7351 C/T); (iii) T-->C in exon 6 (20 099 T/C); and (iv) T-->A (27 445 T/A) in intron 10. RESULTS: Substance P and sodium nitroprusside caused dose-dependent increases in forearm blood flow in all patients (P < 0.001 for all) that were independent of the four genetic polymorphisms. Similarly, there were no differences in basal plasma t-PA antigen concentrations or net t-PA release between genotypes. Compared to non-smokers, smokers exhibited impaired substance P-induced vasodilatation (P < 0.001) and t-PA release (P = 0.05). CONCLUSIONS: Despite confirming our previous findings in cigarette smokers, we have found no effect of polymorphisms of the t-PA gene on two complementary aspects of endothelial function. We conclude that genetic variation of the t-PA locus is unlikely to have a major influence on acute t-PA release in subjects with established CHD.